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Protective Effect of Folic Acid on Oxidative DNA Damage: A Randomized, Double-Blind, and Placebo Controlled Clinical Trial.
Guo, X, Cui, H, Zhang, H, Guan, X, Zhang, Z, Jia, C, Wu, J, Yang, H, Qiu, W, Zhang, C, et al
Medicine. 2015;(45):e1872
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Abstract
Although previous reports have linked DNA damage with both transmissions across generations as well as our own survival, it is unknown how to reverse the lesion. Based on the data from a Randomized, Double-blind, Placebo Controlled Clinical Trial, this study aimed to assess the efficacy of folic acid supplementation (FAS) on DNA oxidative damage reversal.In this randomized clinical trial (RCT), a total of 450 participants were enrolled and randomly assigned to 3 groups to receive folic acid (FA) 0.4 mg/day (low-FA), 0.8 mg/day (high-FA), or placebo (control) for 8 weeks. The urinary 8-hydroxy-2'-deoxyguanosine (8-OHdG) and creatinine (Cr) concentration at pre- and post-FAS were measured with modified enzyme-linked immunosorbent assay (ELISA) and high-performance liquid chromatography (HPLC), respectively. A multivariate general linear model was applied to assess the individual effects of FAS and the joint effects between FAS and hypercholesterolemia on oxidative DNA damage improvement. This clinical trial was registered with ClinicalTrials.gov, number NCT02235948.Of the 438 subjects that received FA fortification or placebo, the median (first quartile, third quartile) of urinary 8-OHdG/Cr for placebo, low-FA, and high-FA groups were 58.19 (43.90, 82.26), 53.51 (38.97, 72.74), 54.73 (39.58, 76.63) ng/mg at baseline and 57.77 (44.35, 81.33), 51.73 (38.20, 71.30), and 50.65 (37.64, 76.17) ng/mg at the 56th day, respectively. A significant decrease of urinary 8-OHdG was observed after 56 days FA fortification (P < 0.001). Compared with the placebo, after adjusting for some potential confounding factors, including the baseline urinary 8-OHdG/Cr, the urinary 8-OHdG/Cr concentration significantly decreased after 56 days FAS [β (95% confidence interval) = -0.88 (-1.62, -0.14) and P = 0.020 for low-FA; and β (95% confidence interval) = -2.68 (-3.42, -1.94) and P < 0.001 for high-FA] in a dose-response fashion (Ptrend < 0.001). Test of interaction between hypercholesterolemia and FA supplementation on urinary 8-OHdG reduction was significant (P = 0.001).The present study demonstrates that FA fortification is independently linked to the reduction of urinary 8-OHdG/Cr in a dose-related pattern, which suggests that FA is beneficial to protect against oxidative damage to DNA. This effect is apparently stronger in those with hypercholesterolemia. The authors provide a new insight into the prevention and reversal of oxidative DNA damage.
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Potential role of oxidative stress on the prescription of rehabilitation interventions in spinal cord injury.
Lam, T, Chen, Z, Sayed-Ahmed, MM, Krassioukov, A, Al-Yahya, AA
Spinal cord. 2013;(9):656-62
Abstract
STUDY DESIGN Review article. OBJECTIVES To provide an overview of free radical biology, particularly with respect to muscle physiology, as well as the potential effects of muscle morphological changes, physical capacity and nutritional status on oxidative stress in people with chronic spinal cord injury (SCI). The potential implications of these factors for determining the optimal dosage of rehabilitation training interventions in people with chronic SCI will also be presented. SETTING Vancouver, BC, Canada. METHODS Literature review. RESULTS Not applicable. CONCLUSION There has been a great deal of focus on rehabilitation exercise interventions providing intensive practice of movements to enhance functional recovery and physical capacity following SCI. However, there is still much to be understood about the appropriate dosage of training parameters (e.g. frequency, duration). It has been known for several decades that exercise increases free radical production, leading to oxidative stress. To date, there has been little consideration of the potential interaction of oxidative stress with training parameters on functional outcomes in chronic SCI. Furthermore, individuals with chronic SCI face many secondary consequences of their injury, such as muscle atrophy, change in muscle fiber type, general deconditioning and nutritional status, that are known to influence free radical production and antioxidant capacity. Better understanding of the potential confounding effects of oxidative stress associated with exercise will improve our ability to determine the optimal 'dose' of rehabilitation training to maximize functional recovery following SCI.